Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

JAMA Neurology, Год журнала: 2024, Номер 81(3), С. 255 - 255

Опубликована: Янв. 22, 2024

Importance Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of tests research and clinical use has been limited. Expanding access this highly accurate AD crucial wider evaluation implementation tests. Objective To determine utility novel commercially available immunoassay plasma detect pathology evaluate reference ranges abnormal amyloid β (Aβ) longitudinal change across 3 selected cohorts. Design, Setting, Participants This cohort study examined data from single-center observational cohorts: cross-sectional Translational Biomarkers in Aging Dementia (TRIAD) (visits October 2017–August 2021) Wisconsin Registry Alzheimer’s Prevention (WRAP) February 2007–November 2020) Sant Pau Initiative on Neurodegeneration (SPIN) (baseline visits March 2009–November 2021). included individuals without cognitive impairment grouped by (AT) status using PET or CSF biomarkers. Data were analyzed June 2023. Exposures Magnetic resonance imaging, Aβ positron emission tomography (PET), PET, cerebrospinal fluid (CSF) biomarkers (Aβ42/40 p-tau immunoassays), (ALZpath pTau217 assay). Main Outcomes Measures Accuracy detecting according baseline status. Results The 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] 282 males [35.9%]). High accuracy was observed identifying elevated (area under curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) (AUC, 0.93-0.97; 0.84-0.99) all These accuracies comparable determining signal. detection 3-range yielded reproducible results reduced confirmatory testing approximately 80%. Longitudinally, values showed an annual increase only Aβ-positive individuals, highest those positivity. Conclusions Relevance found that accurately identified biological AD, biomarkers, cut-offs It detected changes, including at preclinical stage.

Язык: Английский

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Blood biomarkers for Alzheimer’s disease in clinical practice and trials

Nature Aging, Год журнала: 2023, Номер 3(5), С. 506 - 519

Опубликована: Май 18, 2023

Язык: Английский

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Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests

Nature Medicine, Год журнала: 2024, Номер 30(4), С. 1085 - 1095

Опубликована: Фев. 21, 2024

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test perform as well established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry Swedish BioFINDER-2 cohort (n = 1,422) US Charles F. Joanne Knight Alzheimer Disease Research Center (Knight ADRC) 337). Matched CSF samples were with clinically used FDA-approved automated immunoassays for Aβ42/40 p-tau181/Aβ42. The primary secondary outcomes detection brain Aβ or pathology, respectively, using positron emission tomography (PET) imaging reference standard. Main analyses focused on individuals cognitive impairment (mild mild dementia), which is target population available treatments. equivalent classifying PET status, an area under curve (AUC) both between 0.95 0.97. generally superior classification tau-PET AUCs 0.95-0.98. cognitively impaired subcohorts (BioFINDER-2: n 720; ADRC: 50), plasma had accuracy, positive predictive value negative 89-90% 87-88% tests, further improving 95% two-cutoffs approach. Blood demonstrated performance that AD pathology. Use high-performance clinical practice can improve access accurate diagnosis AD-specific

Язык: Английский

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Alzheimer's disease: From immunotherapy to immunoprevention

Cell, Год журнала: 2023, Номер 186(20), С. 4260 - 4270

Опубликована: Сен. 1, 2023

Язык: Английский

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Blood-based biomarkers for Alzheimer’s disease: Current state and future use in a transformed global healthcare landscape

Neuron, Год журнала: 2023, Номер 111(18), С. 2781 - 2799

Опубликована: Июнь 8, 2023

Язык: Английский

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CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease

Nature Medicine, Год журнала: 2023, Номер 29(8), С. 1954 - 1963

Опубликована: Июль 13, 2023

Abstract Aggregated insoluble tau is one of two defining features Alzheimer’s disease. Because clinical symptoms are strongly correlated with aggregates, drug development and diagnosis need cost-effective accessible specific fluid biomarkers aggregates; however, recent studies suggest that the currently available cannot specifically track aggregates. We show microtubule-binding region (MTBR) containing residue 243 (MTBR-tau243) a new cerebrospinal (CSF) biomarker for aggregates compared it to multiple other phosphorylated measures (p-tau181, p-tau205, p-tau217 p-tau231) in independent cohorts (BioFINDER-2, n = 448; Knight Alzheimer Disease Research Center, 219). MTBR-tau243 was most associated tau-positron emission tomography (PET) cognition, whereas showing lowest association amyloid-PET. In combination explained total variance tau-PET burden (0.58 ≤ R 2 0.75) performance predicting cognitive (0.34 0.48) approached (0.44 0.52). levels longitudinally increased unlike CSF p-tau species. aggregate pathology, which may be utilized interventional trials patients. Based on these findings, we propose revise A/T/(N) criteria include as representing (‘T’).

Язык: Английский

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A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases

Nature Aging, Год журнала: 2023, Номер 3(9), С. 1079 - 1090

Опубликована: Авг. 31, 2023

Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed recent approvals of anti-Aβ immunotherapies Alzheimer's disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow reduce the number confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests while classifying patients. We evaluated two-step determining Aβ-PET status mild (MCI) from two independent memory clinic-based cohorts (n = 348). A blood-based model including plasma tau protein 217 (p-tau217), age and APOE ε4 was developed BioFINDER-1 (area under curve (AUC) 89.3%) validated BioFINDER-2 (AUC 94.3%). In step 1, used to stratify low, intermediate high risk positivity. 2, we assumed referral only intermediate-risk CSF Aβ42/Aβ40 testing, whereas 1 alone determined Aβ-status low- high-risk groups. Depending on lenient, moderate stringent thresholds were overall accuracy detecting 88.2%, 90.5% 92.0%, respectively, reducing necessary by 85.9%, 72.7% 61.2%, respectively. secondary analyses, an adapted version led successful validation different p-tau217 immunoassay TRIAD cohort 84). conclusion, using p-tau217-based stratification MCI substantially need testing patients, offering cost-effective strategy clinic settings.

Язык: Английский

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Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Март 16, 2023

As the leading cause of dementia, Alzheimer's disease (AD) is a major burden on affected individuals, their families and caregivers, healthcare systems. Although AD can be identified diagnosed by cerebrospinal fluid or neuroimaging biomarkers that concord with neuropathological evidence clinical symptoms, challenges regarding practicality accessibility hinder widespread availability implementation. Consequently, many people suspected cognitive impairment due to do not receive biomarker-supported diagnosis. Blood have capacity help expand access diagnostics worldwide. One such promising biomarker plasma phosphorylated tau (p-tau), which has demonstrated specificity versus non-AD neurodegenerative diseases, will extremely important inform diagnosis eligibility for therapies recently been approved. This review provides an update diagnostic prognostic performances p-tau181, p-tau217 p-tau231, associations in vivo autopsy-verified pathological hallmarks. Additionally, we discuss potential applications unanswered questions p-tau therapeutic trials, given recent addition toolbox participant screening, recruitment during-trial monitoring. Outstanding include assay standardization, threshold generation verification diverse cohorts reflective wider community attending memory clinics included trials.

Язык: Английский

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Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads

EMBO Molecular Medicine, Год журнала: 2023, Номер 15(5)

Опубликована: Март 13, 2023

Several promising plasma biomarkers for Alzheimer's disease have been recently developed, but their neuropathological correlates not yet fully determined. To investigate and compare independent associations between multiple (p-tau181, p-tau217, p-tau231, Aβ42/40, GFAP, NfL) neuropathologic measures of amyloid tau, we included 105 participants from the Arizona Study Aging Neurodegenerative Disorders (AZSAND) with antemortem samples a postmortem exam, 48 whom had longitudinal p-tau217 p-tau181. When simultaneously including plaque tangle loads, Aβ42/40 ratio p-tau231 were only associated plaques (ρAβ42/40 [95%CI] = -0.53[-0.65, -0.35], ρp-tau231 0.28[0.10, 0.43]), GFAP was tangles (ρGFAP 0.39[0.17, 0.57]), p-tau181 both (ρp-tau217 0.40[0.21, 0.56], ρp-tau181 0.36[0.15, 0.50]) 0.52[0.34, 0.66]; 0.36[0.17, 0.52]). A model combining showed highest accuracy predicting presence change (ADNC, AUC[95%CI] 0.89[0.82, 0.96]) load (R2 0.55), while alone optimal 0.45). Our results suggest that high-performing assays might be an combination to assess Alzheimer's-related pathology in vivo.

Язык: Английский

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Plasma proteomic profiles predict future dementia in healthy adults

Nature Aging, Год журнала: 2024, Номер 4(2), С. 247 - 260

Опубликована: Фев. 12, 2024

Язык: Английский

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